Antihypertensive Effect of Chronic KT3 - 671, a Structurally New Nonpeptide Angiotensin AT_1 - Receptor Antagonist, in Stroke - Prone Spontaneously Hypertensive Rats
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概要
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KT3-671 (2-propyl-8-oxo-1-[(2’-(1<I>H</I>-tetrazole-5-yl)biphenyl-4-yl)methyl]-4, 5, 6, 7-tetrahydrocycloheptimidazole), a structurally new nonpeptide angiotensin AT<SUB>1</SUB>-receptor antagonist, was administered orally and repeatedly to 15-week-old stroke-prone spontaneously hypertensive rats for 7 weeks; and its effects on blood pressure, heart rate, renal function, plasma renin concentration (PRC), plasma aldosterone concentration (PAC) and hypertension-related tissue damage in the brain, heart, kidney and mesenteric artery were investigated. KT3-671 at a dose of 3 or 10 mg/kg, p.o. per day prevented development of hypertension and produced a significant and consistent reduction of blood pressure in a dose-dependent manner. Enalapril at a dose of 10 mg/kg per day produced cardiovascular effects similar to those of KT3-671 at 10 mg/kg. Despite marked reduction in blood pressure, neither KT3-671 nor enalapril affected the heart rate. KT3-671 at 10 mg/kg produced a transient and significant reduction of urinary sodium excretion in the second week, but did not affect renal function at any other time during the experimental period. Both KT3-671 at 10 mg/kg and enalapril at 10 mg/kg produced a significant increase in PRC and showed a tendency to decrease PAC. Repeated administration of KT3-671 reduced the severity of the pathological changes in the kidney. These results suggest that KT3-671 is a potentially useful antihypertensive drug.
- 社団法人 日本薬理学会の論文
- 1995-11-01
著者
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Suzuki Takeshi
Department of Internal Medicine, Nippon Medical School
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Fujii Takeshi
Department of Cardiology, Nihon University Surugadai Hospital
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KAWASHIMA Koichiro
Department of Mechanical Engineering, Nagoya Institute of Technology
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Amano Hideto
Department Of Thoracic And Cardiovascular Surgery
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Suzuki Takeshi
Department Of Anatomy And Cell Biology Gunma University Graduate School Of Medicine
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Kawashima K
Nagoya Inst. Of Technol. Nagoya Jpn
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FUJIMOTO Kazuko
Department of Pharmacology, Kyoritsu College of Pharmacy
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Amano Hideto
Department Of Pharmacology Kyoritsu College Of Pharmacy
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MOCHIZUKI Seiichiro
Research Laboratories, Kotobuki Seiyaku Co., Ltd.
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TOMIYAMA Akira
Research Laboratories, Kotobuki Seiyaku Co., Ltd.
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Tomiyama A
Kotobuki Pharmaceutical Co. Ltd. Nagano Jpn
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Tomiyama Akira
Research Laboratories Kotobuki Pharmaceutical Co. Ltd.
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Mochizuki S
Kotobuki Pharmaceutical Co. Ltd. Nagano Jpn
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Mochizuki Seiichiro
Research Laboratories Kotobuki Pharmaceutical Co. Ltd.
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藤井 健志
共立薬大 薬
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Kawashima Koichiro
Department Of General Education Nagoya University
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Fujii T
Department Of Pharmacology Kyoritsu College Of Pharmacy
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Fujimoto Kazuko
Department Of Phamacology Kyoritsu College Of Pharmacy
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Suzuki Takeshi
Department Of Pharmacology Kyoritsu College Of Pharmacy
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Fujii Takeshi
Department Of Applied Biological Science Faculty Of Science And Technology Science University Of Tok
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Suzuki Takeshi
Department Of Allergy And Rheumatology Graduate School Of Medicine University Of Tokyo
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KAWASHIMA Koichiro
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo
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